The overall objective of Project 4 of this Program Project Grant is to further our understanding of how activation of the vestibular system contributes to sympathetic and cardiopulmonary regulation during orthostatic stress in humans. We hypothesize that the vestibular reflex activation of sympathetic nerve activity, and subsequent peripheral and visceral vascular responses, and respiratory responses are attenuated in humans with a predisposition to orthostatic intolerance (i.e., idiopathic orthostatic hypotension, vestibular deficient subjects, aged, and highly trained endurance athletes). During the past five years, we have gained new insights regarding vestibular regulation of sympathetic nerve activity and respiration in humans. These studies have demonstrated that engagement of the otolith organs increases muscle sympathetic nerve activity while engagement of the semicircular canals increases respiration. Furthermore, studies in older subjects demonstrate an attenuation of both the vestibulosympathetic and vestibulorespiratory reflexes. Because aging is associated with increased orthostatic intolerance, these findings suggest that these vestibular reflexes may play an important role in orthostatic intolerance. We will test the following specific aims in healthy sedentary controls and subjects with a predisposition to orthostatic intolerance: To examine sympathetic and hemodynamic responses to otolith organ stimulation. To examine peripheral (skeletal muscle) and visceral (renal and mesenteric) vascular responses to vestibular stimulation. To examine respiratory responses to vestibular stimulation. The design of these studies will provide new knowledge regarding vestibular regulation of the sympathetic nervous system and respiration in humans. Additionally, these studies will address the hypotheses that the vestibular system contributes to blood pressure regulation during orthostatic stress and that attenuation of these reflexes contributes to impaired postural blood pressure regulation. Results from these studies will provide a better understanding of a heretofore overlooked but important afferent input to efferent regulation of sympathetic nerve activity and respiration during postural stress.